Cholinergic modulation of angiogenesis: role of the 7 nicotinic acetylcholine receptor. Academic Article uri icon

Overview

abstract

  • Pathological angiogenesis contributes to tobacco-related diseases such as malignancy, atherosclerosis and age-related macular degeneration. Nicotine acts on endothelial nicotinic acetylcholine receptors (nAChRs) to activate endothelial cells and to augment pathological angiogenesis. In the current study, we studied nAChR subunits involved in these actions. We detected mRNA for all mammalian nAChR subunits except alpha(2), alpha(4), gamma, and delta in four different types of ECs. Using siRNA methodology, we found that the alpha(7) nAChR plays a dominant role in nicotine-induced cell signaling (assessed by intracellular calcium and NO imaging, and studies of protein expression and phosphorylation), as well as nicotine-activated EC functions (proliferation, survival, migration, and tube formation). The alpha(9) and alpha(7) nAChRs have opposing effects on nicotine-induced cell proliferation and survival. Our studies reveal a critical role for the alpha(7) nAChR in mediating the effects of nicotine on the endothelium. Other subunits play a modulatory role. These findings may have therapeutic implications for diseases characterized by pathological angiogenesis.

publication date

  • October 1, 2009

Research

keywords

  • Cholinergic Agents
  • Endothelial Cells
  • Neovascularization, Pathologic
  • Nicotine
  • Receptors, Nicotinic

Identity

PubMed Central ID

  • PMC3140170

Scopus Document Identifier

  • 70349253983

Digital Object Identifier (DOI)

  • 10.1002/jcb.22270

PubMed ID

  • 19623583

Additional Document Info

volume

  • 108

issue

  • 2